chr11-2776007-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000218.3(KCNQ1):c.1638G>A(p.Ser546Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,572,900 control chromosomes in the GnomAD database, including 33,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S546S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.17 ( 2692 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30787 hom. )

Consequence

KCNQ1
NM_000218.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: -2.43

Publications

42 publications found

Variant links:

Genes affected

KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

KCNQ1 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 1
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Jervell and Lange-Nielsen syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
atrial fibrillation, familial, 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
short QT syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
short QT syndrome type 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Jervell and Lange-Nielsen syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNQ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 11-2776007-G-A is Benign according to our data. Variant chr11-2776007-G-A is described in ClinVar as Benign. ClinVar VariationId is 42488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000218.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNQ1	NM_000218.3	MANE Select	c.1638G>A	p.Ser546Ser	synonymous	Exon 13 of 16	NP_000209.2
KCNQ1	NM_001406836.1		c.1542G>A	p.Ser514Ser	synonymous	Exon 12 of 15	NP_001393765.1
KCNQ1	NM_001406837.1		c.1368G>A	p.Ser456Ser	synonymous	Exon 14 of 17	NP_001393766.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNQ1	ENST00000155840.12	TSL:1 MANE Select	c.1638G>A	p.Ser546Ser	synonymous	Exon 13 of 16	ENSP00000155840.2	P51787-1
KCNQ1	ENST00000335475.6	TSL:1	c.1257G>A	p.Ser419Ser	synonymous	Exon 13 of 16	ENSP00000334497.5	P51787-2
KCNQ1	ENST00000910997.1		c.1635G>A	p.Ser545Ser	synonymous	Exon 13 of 16	ENSP00000581056.1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25516

AN:

152110

Hom.:

2690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.208

AC:

39074

AN:

187994

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.0372

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.203

AC:

287746

AN:

1420672

Hom.:

30787

Cov.:

AF XY:

0.202

AC XY:

141579

AN XY:

702430

show subpopulations

African (AFR)

AF:

0.0363

AC:

1197

AN:

32978

American (AMR)

AF:

0.353

AC:

13246

AN:

37548

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4177

AN:

25334

East Asian (EAS)

AF:

0.294

AC:

11155

AN:

37978

South Asian (SAS)

AF:

0.182

AC:

14634

AN:

80606

European-Finnish (FIN)

AF:

0.187

AC:

9365

AN:

50010

Middle Eastern (MID)

AF:

0.165

AC:

941

AN:

5716

European-Non Finnish (NFE)

AF:

0.203

AC:

221203

AN:

1091428

Other (OTH)

AF:

0.200

AC:

11828

AN:

59074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12484

24968

37452

49936

62420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7846

15692

23538

31384

39230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.168

AC:

25520

AN:

152228

Hom.:

2692

Cov.:

AF XY:

0.169

AC XY:

12606

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0460

AC:

1912

AN:

41550

American (AMR)

AF:

0.287

AC:

4382

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

546

AN:

3472

East Asian (EAS)

AF:

0.291

AC:

1503

AN:

5166

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4830

European-Finnish (FIN)

AF:

0.189

AC:

2001

AN:

10610

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13617

AN:

67992

Other (OTH)

AF:

0.185

AC:

390

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1081

2162

3244

4325

5406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.192

Hom.:

8204

Bravo

AF:

0.174

Asia WGS

AF:

0.220

AC:

763

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Long QT syndrome (3)

Long QT syndrome 1 (2)

Atrial fibrillation, familial, 3 (1)

Cardiac arrhythmia (1)

Cardiovascular phenotype (1)

Congenital long QT syndrome (1)

Jervell and Lange-Nielsen syndrome 1 (1)

not provided (1)

Short QT syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.5

(source)

DANN

Benign

0.93

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over